US3268527A - Process for 2, 4-dialkyl-6-isopropoxy-s-triazine - Google Patents
Process for 2, 4-dialkyl-6-isopropoxy-s-triazine Download PDFInfo
- Publication number
- US3268527A US3268527A US291264A US29126463A US3268527A US 3268527 A US3268527 A US 3268527A US 291264 A US291264 A US 291264A US 29126463 A US29126463 A US 29126463A US 3268527 A US3268527 A US 3268527A
- Authority
- US
- United States
- Prior art keywords
- triazine
- reaction
- dialkyl
- isopropoxy
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms
Definitions
- the present invention is concerned with the preparation of 2,4-dialkyl-6allhoxy-s-triazines and with their use in an improved process for the preparation of 2,4-dialkyl-6- sulfanilamido-setriazines. More particularly, it relates to reacting a Grignard reagent of the formula RMgX, in a solvent medium with an s-triazine of Formula I in Step A of the following reaction scheme to obtain an s-triazine of Formula II which is reacted in Step B with sodium sulfanilamide to obtain s-triazines of Formula III.
- R is a lower alkyl of ,1-4 carbons
- X is usually chlorine or bromine, less often iodine
- (hal) is usually chlorine or bromine but may be iodine.
- Such compounds of Formula III are prepared by the known reaction of a suitable 2,4-dialkyl-6-alkoxy-striazine with sodium sulfanilamide. In that reaction the 6-alkoxy substituent is replaced by the .sul fanilamido group.
- reaction the 6-alkoxy substituent is replaced by the .sul fanilamido group.
- development and use of the products of (III) have been hindered in the past by the difficulty of preparing a suitable intermediate.
- the 2,4-diethyl-6-sulfanilamido-s-triazine noted above, requires as an intermediate a 2,4-diethyl-6-alkoxy-s-triazine. An involved synthesis is required to obtain the intermediate.
- a Grignard reagent is prepared in the usual Way, utilizing a suitable solvent normally employed for the purpose. However, the resultant solution is not used directly as the reaction medium. Instead, a starting triazine of (II) above is separately dissolved in a suitable solvent and the two solutions are then combined to form the reaction medium.
- solvent for the triazine a halogenated aliphatic hydrocarbon such as methylene chloride is preferred. However, if necessary or desirable, other solvents such as toluene, tetrahydrofuran, and the like may be used. Resulting reaction not only produces a better yield of desired product, but reduced amounts of side reaction products.
- Grign-ard reagent means the well-known alkyl magnesium halides of the formula RMgX. They are prepared by standard and well-known procedures using a suitable alkyl halide having the desired value for R. Although the process of this invention is not limited thereto, of primary interest are compounds produced when R is lower alkyl.
- R may be alkyl of from 1 to 18 carbon atoms, of either branched or straight chains, such as methyl, ethyl, propyl, decyl and octadecyl.
- the halide usually will be a bromide or chloride, less often an iodide.
- Useful halides include, for example, methyl chloride, ethyl bromide, n-propyl iodide, isopropyl bromide, secondary butyl bromide, tertiary butyl chloa,2es,527
- the Grignard reagent may be prepared in a solvent normally used for this purpose, e.g., diethyl ether, di-n-butyl ether, tetrahydrofuran and the like.
- the preferred solvents are diethyl ether and tetrahydrofuran.
- Methylene chloride should be present in amount at least half of the total solvent volume of the reaction medium. Below this amount, the yield of dialkyl-s-triazines falls 01f, the decrease being very appreciable when as little as 30% is present. As a maximum there is no particular limit. In general, amounts of from about 50% to about 80% of the total solvent volume is good practice.
- the reactant proportions are not critical. It is found that about one molecular equivalent of the Grignard reagent coordinates with the s-triazine without further participation. Too great an excess, however, seems to favor the competing side reactions. A good practice is to add about 2.5 to about 3.5 mols of the Grignard reagent per mol of s-triazine.
- reaction temperature range should be between about 0 C. and about minus C. Lower temperatures can be used but the advantages do not offset the difficulty.
- Control of reaction time is essential to obtaining optimum results. By the time the second alkylation has taken place and the isopropoxy-dialkyl-s-triazine has formed, it tends to quaternize with itself, forming a polymer. For any one set of reaction conditions such as volume, temperature, stirring efiiciency and the like, there is an optimum time. Exact limits cannot be set to cover all such combinations. In general, however, reaction periods of from about two to about six hours will constitute good practice.
- the products are separated from the reaction mixture by any convenient method. This may include the addition of water to the reaction mixture, followed by separation of the organic solvents containing the products of the reaction.
- Example 2 To illustrate the advantages of an isopropoxy substituent in the 6-position, the procedure of Example 1 was repeated substituting an equimolar amount of 2,4- dichloro-6-methoxy-s-triazine for the 6-isopropoxy-s-triazine. The product contained only 42% of the 2,4-diethyl-6-methoxy-s-triazine, a yield of only 26%.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
United States Patent g 3,268,527 Patented August 23, 1966 The present invention is concerned with the preparation of 2,4-dialkyl-6allhoxy-s-triazines and with their use in an improved process for the preparation of 2,4-dialkyl-6- sulfanilamido-setriazines. More particularly, it relates to reacting a Grignard reagent of the formula RMgX, in a solvent medium with an s-triazine of Formula I in Step A of the following reaction scheme to obtain an s-triazine of Formula II which is reacted in Step B with sodium sulfanilamide to obtain s-triazines of Formula III.
a t /C\ /C\ N N RMgX N N I II I ll hal-O o-oomonm (A) RO o-oornornn sodium sulfanilamide (B) i 0 v T i R-O o-Nn-soz-NH,
(III) wherein in the foregoing Formulae I, II and III, R is a lower alkyl of ,1-4 carbons; X is usually chlorine or bromine, less often iodine; and (hal) is usually chlorine or bromine but may be iodine.
In the past, a number of sulfonamido compounds such as those of Formula III, above, particularly those in which R is a lower alkyl radical of one to four carbon atoms, have become known for use as sulfa drugs. Of particular interest for this purpose, for example, is 2,4-diethyl-6-sulfanilarnido-s-triazine, the compound of Formula 111, when each R is ethyl.
Such compounds of Formula III are prepared by the known reaction of a suitable 2,4-dialkyl-6-alkoxy-striazine with sodium sulfanilamide. In that reaction the 6-alkoxy substituent is replaced by the .sul fanilamido group. However, development and use of the products of (III) have been hindered in the past by the difficulty of preparing a suitable intermediate. For example, the 2,4-diethyl-6-sulfanilamido-s-triazine, noted above, requires as an intermediate a 2,4-diethyl-6-alkoxy-s-triazine. An involved synthesis is required to obtain the intermediate.
Perhaps the best previously-available process for 2,4- dialkyl-6-alkoxy-s-triazines involved the multiple steps of the following reaction sequence:
Sodium acid Methylisourea cyanamlde hydrochloride 0 CzHs C1H CN H01 C H OH C2H5C=NH-HCI P ropionitrile Ethyl propionimidats hydrochloride O C gI-I5 O C 2115 K 2 C O a OQH5CZNHHOI O H5C=NH Ethyl propionimidate Ethyl prohydrochloridc piouimid ate 0 C 2H5 O C H:
O NH
Moreover, these reactions are not readily carried out and some of the intermediate stage products are not too stable. By comparison, the one-step reaction of Step A above according to the present invention offers a far simpler and more satisfactory route to compounds of (III).
As shown in my copending application with Henryk Bader, Serial No. 291,265, filed June 28, 1963; 2,4-dihalos-triazines of Formula I above wherein the substituent in the 6-position is rnethoxy-, ethoxyor n.-propoxy-, in methylene chloride, may be reacted with a Grignard reagent according to Step A above.
This use of a chlorinated aliphatic-hydrocarbon solvent medium, such as methylene chloride, did produce useful results. Unfortunately, the alkoxy group in the 6-po-. sition can also be reacted with the Griignard reagent. This was found to occur to a greater extent than was desirable in the overall process.
It is therefore an object of the present invention to decrease this objectionable production of trialkyl-striazines and other byproducts in Step A. Surprisingly, this has been accomplished by the unexpected discovery that isopropoxy in the 6-position is non-reactive to the degree that Step A produces a greatly improved yield of the desired s-triazine of Formula II above.
A Grignard reagent is prepared in the usual Way, utilizing a suitable solvent normally employed for the purpose. However, the resultant solution is not used directly as the reaction medium. Instead, a starting triazine of (II) above is separately dissolved in a suitable solvent and the two solutions are then combined to form the reaction medium. As solvent for the triazine, a halogenated aliphatic hydrocarbon such as methylene chloride is preferred. However, if necessary or desirable, other solvents such as toluene, tetrahydrofuran, and the like may be used. Resulting reaction not only produces a better yield of desired product, but reduced amounts of side reaction products.
As so described, however, the simplicity of the pro cedure is more apparent than real. A number of factors must be given careful consideration and control. Otherwise, optimum results are not obtainable. Accordingly, each will be considered separately.
In this discussion it should be understood that the term Grign-ard reagent :means the well-known alkyl magnesium halides of the formula RMgX. They are prepared by standard and well-known procedures using a suitable alkyl halide having the desired value for R. Although the process of this invention is not limited thereto, of primary interest are compounds produced when R is lower alkyl.
As defined generally, above, R may be alkyl of from 1 to 18 carbon atoms, of either branched or straight chains, such as methyl, ethyl, propyl, decyl and octadecyl.
The halide usually will be a bromide or chloride, less often an iodide. Useful halides include, for example, methyl chloride, ethyl bromide, n-propyl iodide, isopropyl bromide, secondary butyl bromide, tertiary butyl chloa,2es,527
3 ride, n-hexyl iodide, 1,1-diethyl-n-propyl bromide, and the like. The Grignard reagent may be prepared in a solvent normally used for this purpose, e.g., diethyl ether, di-n-butyl ether, tetrahydrofuran and the like. The preferred solvents are diethyl ether and tetrahydrofuran.
Either mode of mixture of reactant, addition of solution of s-triazine to Grignard solution or vice versa, is satisfactory. As to the chlorinated aliphatic hydrocarbon solvent or suspending medium in which the starting triazine is placed, before addition thereto of the Grignard reagent, methylene chloride is preferred for several reasons. Other methylene halides are not as readily available. Longer alkylene chain halides are generally not as elfective in solvent power for the triazine and are less readily evaporated.
Methylene chloride should be present in amount at least half of the total solvent volume of the reaction medium. Below this amount, the yield of dialkyl-s-triazines falls 01f, the decrease being very appreciable when as little as 30% is present. As a maximum there is no particular limit. In general, amounts of from about 50% to about 80% of the total solvent volume is good practice.
As to the reactant proportions, they are not critical. It is found that about one molecular equivalent of the Grignard reagent coordinates with the s-triazine without further participation. Too great an excess, however, seems to favor the competing side reactions. A good practice is to add about 2.5 to about 3.5 mols of the Grignard reagent per mol of s-triazine.
Conducting the reaction at temperatures below C. is very important. While monoalkyl-s-triazines can be prepared at temperatures above 0 C., the next alkylation step is favored by low temperatures. Above about 0 C. competing reactions are faster than the second alkylation; below 0 C. the side reactions occur to less' extent than does the second alkylation. In general, the reaction temperature range should be between about 0 C. and about minus C. Lower temperatures can be used but the advantages do not offset the difficulty.
Control of reaction time is essential to obtaining optimum results. By the time the second alkylation has taken place and the isopropoxy-dialkyl-s-triazine has formed, it tends to quaternize with itself, forming a polymer. For any one set of reaction conditions such as volume, temperature, stirring efiiciency and the like, there is an optimum time. Exact limits cannot be set to cover all such combinations. In general, however, reaction periods of from about two to about six hours will constitute good practice.
When the reaction is completed, as indicated by the disappearance of the Grignard reagent according to wellknown test procedures, the products are separated from the reaction mixture by any convenient method. This may include the addition of water to the reaction mixture, followed by separation of the organic solvents containing the products of the reaction.
' The invention will be further illustrated in conjunction with the following examples. Therein all parts and percentages are by weight and temperatures are in degrees centigrade, unless other-wise noted. Parts by volume are to the parts by weight as milliliters and grams of water are to each other.
4% Example 1 To 260 parts by volume of a 3.46 molar solution of ethylmagnesium chloride (0.90 mole) in tetrahydrofuran, there is slowly added 62.4 parts (0.30 mole) of 2,4-dichloro-6-isopropoxy-s-triazine in 600 parts of methylene chloride at a temperature in the range of minus l5- 4 C. The reaction mixture is stirred for about 6 hours, whereupon parts of Water is added and the organic solution is collected. Evaporation of the solvent gives 32.6 parts of material analyzing 73.8% of 2,4-diethyl-6- isopropoxy-s-triazine (41.2% yield).
Example 2 To illustrate the advantages of an isopropoxy substituent in the 6-position, the procedure of Example 1 was repeated substituting an equimolar amount of 2,4- dichloro-6-methoxy-s-triazine for the 6-isopropoxy-s-triazine. The product contained only 42% of the 2,4-diethyl-6-methoxy-s-triazine, a yield of only 26%.
I claim:
1. In a process :for the preparation of a dialky-l-s-triazine which comprises reacting a Grignard reagent of the formula RMgX, where R is lower alkyl and X is selected from the group consisting of chlorine, bromine and iodine, with a 2,4-dihalo-s-triazine; the improvement which consists in carrying out the reaction using an s-triazine of the formula (hal) wherein (hal) is a halogen.
2. A process according to claim 1 in which (hal) is chlorine.
3. A process according to claim 1 in which (hal) is bromine.
4. A process according to claim 1 in which R is ethyl and (hal) is chlorine.
5. A process according to claim 1 in which R is ethyl and (hal) is bromine.
6. A process according to claim 1 in which a solution of the Grignard reactant in the solvent in which it is prepared is combined with a solution of the s-triazine in methylene chloride to form the reaction mixture.
7. A process according to claim 6 in which the reagent mixture is agitated at ambient temperature until substitution of both Rs is substantially completed and thereafter the reaction stopped before quaternization of a substantial amount of the resultant product occurs.
Claims (1)
1. IN A PROCESS FOR THE PREPARATION OF A DIALKYL-S-TRIAZINE WHICH COMPRISES REACTING A GRIGNARD REAGENT OF THE FORMULA RMGX, WHERE R IS LOWER ALKYL AND X IS SELECTED FROM THE GROUP CONSISTING OF CHLORINE, BROMINE AND IODINE, WITH A 2,4-DIHALO-S-TRIAZINE; THE IMPROVEMENT WHICH CONSISTS IN CARRYING OUT THE REACTION USING AN S-TRIAZINE OF THE FORMULA
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US291264A US3268527A (en) | 1963-06-28 | 1963-06-28 | Process for 2, 4-dialkyl-6-isopropoxy-s-triazine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US291264A US3268527A (en) | 1963-06-28 | 1963-06-28 | Process for 2, 4-dialkyl-6-isopropoxy-s-triazine |
Publications (1)
Publication Number | Publication Date |
---|---|
US3268527A true US3268527A (en) | 1966-08-23 |
Family
ID=23119602
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US291264A Expired - Lifetime US3268527A (en) | 1963-06-28 | 1963-06-28 | Process for 2, 4-dialkyl-6-isopropoxy-s-triazine |
Country Status (1)
Country | Link |
---|---|
US (1) | US3268527A (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3083242A (en) * | 1956-09-19 | 1963-03-26 | M & T Chemicals Inc | Preparation of certain organomagnesium chlorides in ethylene polyethers |
-
1963
- 1963-06-28 US US291264A patent/US3268527A/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3083242A (en) * | 1956-09-19 | 1963-03-26 | M & T Chemicals Inc | Preparation of certain organomagnesium chlorides in ethylene polyethers |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US3206494A (en) | Cyclic phosphonitriles and process for preparing same | |
US3268527A (en) | Process for 2, 4-dialkyl-6-isopropoxy-s-triazine | |
US3100215A (en) | Process for preparing liquid hexaalkyl-distannoxanes | |
US3393253A (en) | Ureidophosphonates and preparation thereof | |
Cucinella et al. | The chemistry and the stereochemistry of poly (N-alkyliminoalanes): IX. Hexameric organoaluminum imides by reaction of (HAIN-iso-C3H7) 6 with trialkylaluminums | |
US4613703A (en) | Process for allylating hydroxyaromatic compounds | |
SU535910A3 (en) | The method of obtaining Tris- (2-chloroethyl) phosphite | |
Smith et al. | Regiospecific synthesis of 1-substituted 1, 2, 4-triazoles involving isomerization of the corresponding 4-substituted compounds. | |
US3086056A (en) | Phosphines | |
Willemsens et al. | Investigations on organolead compounds VIII. Reactions of (triorganoplumbyl) metal reagents With polychloromethanes; Tetrakis (triphenylplumbyl) methane and related compounds | |
US3959376A (en) | Production of 4-halo-2-alkenyl tri-lower alkyl ammonium or phosphonium halides | |
US3399236A (en) | Ammonolysis of alkyl halides | |
US4074052A (en) | Process for preparation of isocyanuric acid triesters | |
US2488336A (en) | Production of nu-alkyl pyrroles | |
US3928370A (en) | Process for making dialkyl pyridylphosphates | |
US3285981A (en) | Production of alpha, omega-substituted alkanes | |
JPH0321021B2 (en) | ||
Zimmer et al. | Sterically Hindered Group IV-A Organometallics. V. 1a-d Preparation and Properties of Certain Neopentyl-and Neophylleads1e | |
US3914252A (en) | Preparation of N-iodocompounds | |
US2628237A (en) | Alkali metal salts of isonicotinylhydrazinomethanesulfinic acid | |
US3625964A (en) | Production of metal salts of diorgano substituted isocyanurates | |
US12071399B2 (en) | Process for the preparation of arylsulfonylpropenenitriles | |
US3150138A (en) | Method of preparing monoquaternary nitrogen compounds | |
US2765333A (en) | Bis(cyanopentenoxy) alkanes and their preparation | |
US3478095A (en) | Preparation of phosphonamides |